Elecoglipron Produces Significant Weight Loss and Improves Glycemic Control in Phase II Trials
Treatment with the investigational oral GLP-1 receptor agonist elecoglipron resulted in meaningful weight loss in individuals with obesity and improved glucose control in patients with type 2 diabetes, according to findings from two global Phase II randomized trials. In the dose-ranging VISTA study, which enrolled adults with obesity or overweight without diabetes, mean weight loss at 26 weeks increased progressively with higher doses of elecoglipron, ranging from 2.6% in the 5 mg group to 10.5% in the 75 mg group using weekly dose escalation. By comparison, participants receiving placebo experienced only a 0.6% reduction in body weight. These results highlight elecoglipron's potential as an effective oral therapy for obesity and metabolic disorders, supporting its continued development in larger clinical trials. The study was published in The Lancet by Melanie J Davies and colleagues.
A robust phase 2 dose-ranging trial was carried out in selected medical research institutions and hospitals located in Australia, Canada, Germany, Japan, Taiwan, the United Kingdom, and the United States. The study recruited adult subjects, who were aged 18 years or above, with a BMI score of 30 kg/m² or higher or at least 27 kg/m² if associated with at least one condition related to obesity. Subjects with any existing type 2 diabetes diagnosis before participation were excluded. Patients were randomly assigned to six groups with an intricate 2:3:3: 3:3:5 ratio to either placebo tablets or any of five different oral dosing regimens involving elecoglipron: 5 mg or 15 mg without titration, 50 mg up-titration at 4-week intervals, 75 mg titration weekly, or 75 mg up-titration every two weeks.
The treatment period lasted for 36 weeks; participants, treating doctors, and the funding organization were all blinded. The main criteria used to determine the efficacy of elecoglipron included percentage changes in body weight measured from the beginning of the treatment and the proportion of individuals with a 5% or greater weight reduction at week 26. The study was registered under NCT06579092.
Key findings:
- A total of 472 patients had been screened from October 8, 2024, to February 18, 2025, while a total of 310 patients managed to be randomized to the different treatment regimens.
- Out of the 310 randomized patients, 288 patients (93%) successfully concluded a period of 36 weeks, while 231 patients (75%) managed to adhere to the designated treatment protocol.
- The randomized patient population was aged an average of 48.4 years (SD 13.7), with an average bodyweight of 106.9 kg (SD 24.1) and an average BMI of 38.2 kg/m² (SD 7.2).
- Among the randomized patients, there were 225 female patients (73%) and 85 male patients (27%).
- The estimated mean change from baseline in total body weight at Week 26 varied from -2.6% for the low dose of 5 mg elecoglipron to -10.5% in the high dose of 75 mg weekly titration treatment regimen, compared to -0.6% in the placebo arm.
- The estimated proportion of patients meeting the criterion of 5% or more weight loss at Week 26 varied between 40.4% and 88.8% among the different active elecoglipron treatment arms against 15.6% in the placebo arm.
Conclusively, daily oral administration of elecoglipron showed a significant amount of weight loss with safety and tolerability comparable to those seen with other drugs in its class of GLP-1 receptor agonists, indicating the need for phase 3 trials in patients suffering from obesity or overweight conditions. The good results recorded here can help in the development of future metabolism therapies, showing that oral molecules have the capability of achieving the same weight loss witnessed only through injections before.
Reference:
Davies, M. J., Aroda, V. R., Rosenstock, J., Capehorn, M., Pedersen, S. D., Morizzo, E., Malhotra, S., Johansson, P. A., Grice, D., Andersson, A., Rizi, E. P., & Sjöström, C. D. (2026). Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA): a multicentre, phase 2, randomised, placebo-controlled clinical trial. Lancet. https://doi.org/10.1016/S0140-6736(26)00748-8
